Cytokines belong to a large group of polypeptide- or glycopeptide-signaling molecules that act, at extremely low concentrations, as regulators of cell growth and essential mediators of inflammation and immune reactions. The production and functions of cytokines are tightly regulated by cytokines themselves and by several other factors. Most cytokines act locally and are implicated in a number of inflammatory conditions. These include rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis, psoriasis, ulcerative colitis and Crohn's disease.
The antimalarial compounds chloroquine and hydroxychloroquine are known as broadly active, modestly potent inhibitors of cytokines. Such antimalarial agents have become important disease-modifying antirheumatic agents (DMARD) in the second line treatment of rheumatoid arthritis and other inflammatory disorders. Other agents in this class include gold, penicillamine, methotrexate and cyclosporins, all of which have potent activity. However, the utility of these latter drugs for the treatment of a chronic disease such as rheumatoid arthritis is limited by serious side-effects. The antimalarial agents in the DMARD class are recognised as having a more moderate side-effect profile, while possibly lacking the potency of some of the other agents. However, there is still concern about the ocular side-effects of both chloroquine and hydroxychloroquine. Thus, it may be postulated that a drug for the treatment of arthritis that possesses an improved efficacy versus side-effect profile over hydroxychloroquine, the most significant antimalarial drug in the DMARD class, would be of significant clinical potential.
In terms of antimalarial potency, mefloquine is one of the most effective drugs indicated for both prophylaxis and treatment and has particular utility for use in chloroquine-resistant malaria. Chloroquine has been the mainstay of antimalarial treatment and prophylaxis, but the emergence of chloroquine resistance in Plasmodium falciparum, the most lethal strain, has started to limit its utility. Thus mefloquine has emerged as the preferred compound for the prophylaxis and treatment of malignant malaria.
Mefloquine enantiomers have been evaluated in animal models for efficacy against Plasmodium species. These studies concluded that there was no difference in antimalarial potency of the enantiomers.